1. Field of the Invention
The present disclosure relates to an aptamer. More particularly, the present disclosure relates to an aptamer that specifically targets a peptide presented by a major histocompatibility complex (MHC) on the cell surface.
2. Description of Related Art
Aptamers are oligonucleotides, such as ribonucleic acid (RNA) and single-stranded deoxyribonucleic acid (ssDNA), or peptide molecules that can bind to their targets with high affinity and specificity due to their specific secondary and tertiary structures. Generally, the oligonucleotide aptamers are identified from an initial library containing 1013-1016 random RNA or ssDNA sequences through an in vitro selection process termed systematic evolution of ligands by exponential enrichment or the so-called “SELEX procedures.”
Like antibodies, oligonucleotide aptamers can be used for both basic research and clinical purposes due to their target-binding specificity. Compared to antibodies, oligonucleotide aptamers offer various advantages, which include, (1) economical synthesis and flexible modification: oligonucleotide aptamers, once selected, can be synthesized in quantity and modified to fulfill various designed purposes via chemical reaction; (2) high stability: oligonucleotide aptamers exhibit long-term stability as dry powders and once dissolved in solution, they are also thermally stable and structurally reversible to their native conformation even after denaturation; (3) high biocompatibility: based on the nucleic acid recognized as self-antigen by immune system, oligonucleotide aptamers are usually low-toxic and low-immunogenic molecules; and (4) rapid tissue penetration: as nucleic acids, oligonucleotide aptamers could easily penetrate and thus bind to the intracellular targets by transfection reagents. These physical and chemical properties make oligonucleotide aptamers a potential targeting-tool to replace antibodies in research, diagnostic platforms, drug discovery, and therapeutics.
Since tumor-associated antigens (TAAs) are only expressed in tumor/cancer cells, they can be considered as tumor markers useful in identifying, labeling, or treating tumor/cancer cells. Melanoma-associated antigen A3 (MAGE-A3) is one of the most frequently and highly expressed TAAs in tumors. It is expressed in 74% of metastatic melanomas, 57% of esophageal carcinoma, 38% of gastric carcinoma, 39% of lung cancer, 33% of multiple myeloma. The expression of MAGE-A3 is also seen in various other types of cancer, including bladder, breast, pancreatic, renal, hepatocellular, and head and neck squamous cell carcinoma. Further, the expression of MAGE-A3 often relates to malignancy and poor prognosis. Therefore, in the fields of cancer therapy or tumor diagnosis, MAGE-A3 serves as a useful marker to precisely and simultaneously target various types of tumors at various stages.
Several epitopes of MAGE-A3 have been identified, and both MHC classes I and II present these antigens. Multiple MAGE-A3 peptide fragments in the region of amino acids 111-126, identified in various tumors, have been associated with a broad set of HLA (human MHC locus) molecules, including alleles of HLA-A, HLA-B, HLA-DP, and HLA-DR, as predominantly observed in various ethnic groups. Thus, these antigens are good candidates for targeting a large population of cancer patients.
In view of the foregoing, there exists a need in the related art an aptamer capable of recognizing a tumor-associated MAGE-A3 peptide with desirable specificity and affinity.